The objective of this program is to validate a new animal model for virus-initiated autoimmunity using our colony of congenic Lew.IWR1 rats. Preliminary data demonstrate that this laboratory strain is susceptible to induction of autoimmune diabetes by a variety of methods including intraperitoneal injection of rat parvovirus (KRV), antibody depletion of regulatory T cells, administration of low dose Poly I:C, and injection of rat cytomegalovirus (RCMV). To our knowledge, this is the first report of induction of diabetes by a cytomegalovirus in a rat model. Further, we have observed that co-infection of rats with RCMV and KRV alters the incidence of diabetes. To commercialize these observations for our contract research services, we must fully characterize this new animal model. To do so, we will first determine the optimum dose and preparation of virus. We will then perform a time course experiment to completely characterize the incidence of diabetes, associated immune response and replication of virus. Finally, we will begin to characterize the mechanism by which RCMV induces diabetes by determining whether diabetogenic T cells are activated after infection. The end result will be a carefully characterized, well defined model system for evaluation of antiviral agents and therapies directed against environmentally-induced diabetes for use by biopharmaceutical companies worldwide.